FEV1/FEV1pp, FVC/FVCpp, FEV1_FVC, pctEmph_Slicer, TLCpp, finalGoldSmokCigNow, CigPerDayNow > 15, CompletedSchool > 237K long (>10kb) local ancestry segments (Parker et al. 2014)
The COPDGene data is appropriate, as the proportion of (global) African ancestry was shown to be associated with the risk of COPD
Confounding factors other that global ancestry \(a_g\):
FEV1 ~ Age + Age^2 + Gender + Height + PackYears + SmokCigNowpctEmph_Slicer traitThis (marginal) model was used in (Parker et al. 2014).
Is it OK for interaction?
SmokCigNow + ATS_PackYears → Duration_Smoking + log_CigPerDaySmokAvg + SmokCigNow + SmokCigNow0_15 + SmokCigarNowMore details in our previous talk COPDGene African-Americans & QQ plots
SmokCigNow (7 traits)\(z = [z_1; z_2; \dots]^T \sim N(0, \Sigma)\)
under the null hypothesis
2.5Bonferroni 0.05 / 37K = 1.4e-06
Ancestry segment: 11:12,332,105 - 12,394,102
Genes: PARVA, MICAL2, MICALCL, RASSF10, TEAD1
| Trait | Exposure | z-score | p-value |
|---|---|---|---|
| FEV1pp | SmokCigNow | 4.5 | 7.3e-06 |
| FEV1_FVC | SmokCigNow | 3.9 | 1.1e-04 |
| FEV1 | SmokCigNow | 3.8 | 1.4e-04 |
| Trait | Exposure | z-score | p-value |
|---|---|---|---|
| FEV1 | SmokCigNow0_15 | 4.2 | 2.6e-05 |
| FEV1pp | SmokCigNow0_15 | 4.1 | 4.9e-05 |
| FVC | SmokCigNow0_15 | 4.0 | 6.9e-05 |
| FVCpp | SmokCigNow0_15 | 3.7 | 2.5e-04 |
Parker et al. 2014. “Admixture mapping identifies a quantitative trait locus associated with FEV1/FVC in the COPDGene Study.” Genetic Epidemiology 38 (7): 652–59. doi:10.1002/gepi.21847.
Sul et al. 2016. “Accounting for Population Structure in Gene-by-Environment Interactions in Genome-Wide Association Studies Using Mixed Models.” PLoS Genetics 12 (3): e1005849. doi:10.1371/journal.pgen.1005849.
Zaitlen et al. 2014. “Leveraging population admixture to characterize the heritability of complex traits.” Nature Genetics 46 (12). Nature Publishing Group: 1356–62. doi:10.1038/ng.3139.